1. Field of the Invention
The present invention describes a re-usable pulmonary or nasal inhaler employing capsules of simple construction and operation and low cost.
Inhalers used for the delivery of pharmaceutical compounds are widely known and they are used for the delivery of several types of medicines treating lung disease and as well as for systemic delivery. Several types of inhalers are known, from those comprising a dosing valve and a pressurized canister invented by Charles Thiel in 1956, to nebulizers and powder-based inhalers. This latter category includes reservoir-based devices, containing a bulk container of powder from which several doses may be dispensed, or a supply of unit-doses packaged in blisters, or simple capsules which are loaded by the patient, cut by the device and which deliver the dose of medicinal powder under the suction of patient's inspiratory effort. The present device is in this last category.
Inhalation delivery presents several technical challenges in relation to oral delivery for buccal, stomach or intestinal absorption, or injection delivery, for the simple reason that the respiratory system is designed to prevent powders, dusts or particles from reaching the lung. In addition, powders with optimal inhalation characteristics namely a very small particle size in the range of 2 to 3 micron in diameter are subject to strong cohesive and adhesive forces which prevent the dose from being adequately dispersed and properly deposited in the bronchi, bronchioles and alveoli. In addition, patient compliance is considerably influenced by the ease of use of the device.
2. Discussion of Background Information
In the field of dry powder inhalers, these challenges have been addressed by two major inventive trends. One has favoured the development of sophisticated and mechanically complex devices and the second prefers a minimalist approach, where simple construction combined with advances in powder technology allows high dispersion leading to high lung deposition and therefore good efficacy, as well as easy use and low cost. We believe this option is the most useful.
The prior art includes many references to capsule-based, re-usable, devices. Indeed Allen & Hanbury's Rotahaler (U.S. Pat. No. 4,889,114) is one early embodiment, with extreme simplicity, but where the delivery performance, particularly the emitted dose, was low and highly variable. Others also described inhalers of the same type, such as GB 1,182,779, Spinhaler; U.S. Pat. No. 4,889,114, Inhalator; FR 75 21844, Cyclohaler; PT 101450; US 2003/131847; WO 2004/082750; WO 2007/098870; WO 2007/144659; WO 2009/139732; US 2009/194105), but the addition of metal cutting means or the necessity to add springs made assembly more complicated and increased cost. More recently, Tsutsui (US 2007/0283955) has proposed very simple inhaler where both ends of the capsule are cut and the domes of the capsule are removed. However, in this design extra components need to be added to prevent the powder from spilling out of the device under gravity and Tsutsui's solution has been to add a valve which blocks this spillage and in use, rises when a suction flow is applied so that air may be admitted to the capsule and disperse and entrain the powder into the mouthpiece. The disadvantage in this invention is that under repeated use, powder will slowly accumulate in the valve mechanism and interfere and ultimately prevent the normal operation of the valve, blocking the operation of the inhaler. Beller (WO 2007/093149) proposes a very similar device. Ideally, inhalers must be simple, deliver reproducible doses and solve the problem of powder interference without resorting to valve mechanisms.
Such interaction between powder, which has a natural tendency to invade mechanical components, and the normal operation of inhalers is impacted by the very fine particle size and increasingly by the dose quantity itself. Whereas the medicines to be delivered by inhalation were typically very potent asthma and emphysema drugs (anti-cholinergics, anti-inflammatory corticosteroids and broncho-dilating beta2-agonists) dosed in the range of micrograms and blended with excipients to achieve total powder doses historically ranging from 5 to 25 mg of total formulated doses, drugs being presently developed for inhalation, such as antibiotics for lung infection, are targeting much higher doses, of 50 to 100 mg of pure drug, to which excipients may then be added. With such high doses, the opportunity for device components to fail because of powder ingress is thus much higher. This means that even if an inhaler has successfully addressed the issue of spilling or leaking powder, it must still be designed to divert and channel out any excess powder which may accumulate under repeated use. This would be benefit.
In terms of the cutting means of the capsule, several designs have been proposed (FR 75 21844; EP 1,245,243; U.S. Pat. No. 6,470,884; US 2007/0283955; WO 2009/117112), but they employ needles or blades which have shortcomings. Most cut the capsule to produce a gaping hole, which allows very good air flow, but does not prevent the powder from spilling out of the capsule immediately prior to use. In any case, air and powder passage holes which are too large provide for a delivery that is too rapid and does not allow the powder agglomerates from becoming successfully dispersed. Consequently, there is the need for an inhaler where the geometry and size of the holes will be sufficiently small to prevent powder spillage, conveniently restrict the passage of air to allow a gradual delivery, effective dispersion and delivery.
In addition, the prior art infrequently refers to the manufacturing method of the cutting means or materials, whereas they have one of the highest impacts on manufacturing cost, on the one hand, and the quality of the cut on the capsule, on the other. In addition, the geometry of the cutting edge is absent from the prior art of inhalers. In this respect, there is the need to develop an inhaler where the cutting means would be optimized for cutting, at the lowest possible cost.
In actuating the capsule, the inhalers of the prior art require a considerable number of steps, due to their mechanical complexity (WO 2007/098,870). The Handihaler inhaler (WO 2009/013218) makes the patient operate the device trough two opening moves, a loading move, a closing move and a piercing move (5 steps) before inhalation. The Cyclohaler inhaler (FR 75 21844) saves on one opening step. There is an opportunity for a device which would only have three steps to inhalation: open, load, close.
The engineering dilemma in such devices is that the inventor is tempted to address operational challenges by increasing the mechanical complexity of the device, detrimentally increasing the complexity of assembly, manufacturing cost, long term reliability and efficacy of the device. The device of the present invention achieves efficiency, reliability, low manufacturing cost and ease of use, by addressing all of the shortcomings identified above. To achieve such a result in a capsule based device with two components only is novel in its own right.